Molecular imaging using radio-labeled agents is gaining popularity and is used both with humans and for laboratory animals, in research and in clinical praxis. The basic principle is that a substance of interest, such as an antibody is labeled with a radiographic tracer. In principle the substance can thus be traced in the body in real time by detecting the decay of the tracer. For an overview of the field see for example: J. Bushberg et al. “The Essential Physics of Medical Imaging”, Second Edition, page 587-736 including references therein and in T. Budinger et al. “Imaging Transgenic Animals”, Annu. Rev. Biomed. Eng. 1999 01, p 611-648 or M. King et al. “Introduction to the physics of molecular imaging with radioactive tracers in small animals, Journal of Cellular Biochemistry Supplement 39 (2002) p. 221-230.
Basically molecular imaging can be used to solve a host of experimental problems that emerge from contemporary biomedical research. Among the areas of greatest promise are the study of small animal models of human diseases, characterizing gene expression and phenotype changes arising from genetic manipulations and maybe most of all applications in drug discovery and development. For further details see J. Fowler et al., “PET and drug research and development”, Journal of Nuclear Medicine 1999: 40(7):1154-1163 and S. Gambihr et al. “Imaging adenoviral-directed reporter gene expression in living animals with positron emission tomography”, Proc of the National Academy of Sciences 1999: 96 p 2333-2338.
One variation of molecular imaging, so called Single Photon Emission Computed Tomography (SPECT), uses a radioactive nuclide emitting x-rays or gamma rays. Common tracers are Technetium (99m) at 140 keV but also tracers like Iodine (125) emitting at lower energies around 30 keV are used. This method is further described in H. Barret and K. Myers “Foundations of Image Science” p 1153-1234. In F. Beekman et al. “U-SPECT-I: A Novel System for Submillimeter-Resolution Tomography with Radiolabeled Molecules in Mice Journal of Nuclear Medicine” Vol. 46 No. 7 1194-1200 an assembly of multiple pinholes for SPECT is outlined.
Another variation of molecular imaging is so called Positron Emission Tomography (PET) where a radioactive nuclei is emitting a positron which, after traveling a short distance annihilate and the resulting 511 keV radiation is emitted back-to-back from the annihilation. The distance the positron travels before annihilation is limiting the spatial resolution. Applications of PET is further described in e.g. B. Solomon et al. “Applications of Positron Emission Tomography in the Development of Molecular Targeted Cancer Therapeutics”, Biodrugs 2003, 17(5) page 339-354, by A. Shukla et al. “Positron emission tomography: An overview”, 2006: 31 (1), Page : 13-21 or W. Moses “Trends in PET imaging”, Nuclear Instruments and Methods in Physics Research A 2001 (471) p 209-214.
It is common practice that the nuclear image is merged with a standard 3D CT transmission image in order to obtain the functional and the structural information in one image and thus being able to locate the functional information more accurately in the body, see e.g. G. Kastis et al. “Compact CT/SPECT Small Animal Imaging System, Trans Nucl Sci 2004; 51: 63-71.
A major challenge with these methods is to achieve sufficient statistics, i.e., a large enough number of counts to limit the statistical noise in a voxel in the image in a reasonable image acquisition time. Normally, an image with minimum image acquisition time, low noise and high spatial resolution is desirable, and these requirements conflict with each other since shorter image acquisition time means less statistics (more noise) and high spatial resolution requires low noise. In today's state-of-the art SPECT equipment, a collimator, pin-hole or so called coded aperture is required to obtain the required spatial resolution. The collimators and pin-holes all have the drawback of very low geometrical acceptance of incident radiation which leads to a decreased number of detected photons and increased noise. The higher spatial resolution required, the further away the pin-hole needs to be from the object, the lower the geometrical acceptance, and the higher the noise. Some of the trade-offs with pinhole imaging are outlined further by S. Metzler et al., “Analytic Determination of Pinhole Collimator Sensitivity with Penetration”.
One way to solve the problem would be to increase the number of injected tracer molecules. However, this number is limited for several practical reasons and because the maximum radiation dose to the object needs to be minimized. Secondly, in the case of single photon emission imaging a collimator, made of an x-ray absorbing material is used to obtain position resolution and this collimator is very inefficient with a transmission often less than 1:1000. Alternatively different pinhole geometries can be used and/or coded apertures but in all cases the transmission efficiency is very low and there is a strong built in trade-off between the spatial resolution and the efficiency. This is e.g. discussed by S. Meikle et al., “CoALA-SPECT: a coded aperture laboratory animal SPECT system for preclinical imaging”, IEEE Nuclear Science Symposium Conference Record, 10-16 Nov. 2002 (2), p. 1061-1065.
One way to mitigate the problem is outlined in U.S. Pat. No. 6,949,748 where the x-rays emitted from the object are focused by means of grazing-incidence optics. These mirrors are bulky and difficult and expensive to manufacture which makes them hard to use in real applications. The mirrors are also hard to align. Moreover the mirrors cannot be positioned next to each other in such a way that they cover a substantial area without leaving a significant amount of dead area between the mirrors.